Rifampin and Rifaximin Resistance in Clinical Isolates of Clostridium difficile

作者：Jennifer R. O’Connor, Minerva A. Galang, Susan P. Sambol, David W. Hecht, Gayatri Vedantam, Dale N. Gerding, Stuart Johnson · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2008 · DOI：10.1128/aac.00342-08 · 被引用次数：188 · 研究领域：Clostridium difficile and Clostridium perfringens research、Microscopic Colitis、Nosocomial Infections in ICU

Rifaximin, a poorly absorbed rifamycin derivative, is a promising alternative for the treatment of Clostridium difficile infections. Resistance to this agent has been reported, but no commercial test for rifaximin resistance exists and the molecular basis of this resistance has not been previously studied in C. difficile. To evaluate whether the rifampin Etest would be a suitable substitute for rifaximin susceptibility testing in the clinical setting, we analyzed the in vitro rifaximin susceptibilities of 80 clinical isolates from our collection by agar dilution and compared these results to rifampin susceptibility results obtained by agar dilution and Etest. We found rifaximin susceptibility data to agree with rifampin susceptibility; the MICs of both antimicrobials for all isolates were either very low or very high. Fourteen rifaximin-resistant (MIC, > or = 32 microg/ml) unique isolates from patients at diverse locations in three countries were identified. Molecular typing analysis showed that nine (64%) of these isolates belonged to the epidemic BI/NAP1/027 group that is responsible for multiple outbreaks and increased disease severity in the United Kingdom, Europe, and North America. The molecular basis of rifaximin and rifampin resistance in these isolates was investigated by sequence analysis of rpoB, which encodes the beta subunit of RNA polymerase, the target of rifamycins. Resistance-associated rpoB sequence differences that resulted in specific amino acid substituti...